Death-bed prophecy

What's left to learn about aging? The burning question for many researchers is whether life-stretching pathways and genes from model organisms boost human life span. Researchers might be able to track down additional genes and pathways that adjust longevity by studying a broader range of organisms or by tracking the evolution of genes that promote aging. An alternative way to extend our lives might be to identify the genes behind late-life killers such as heart disease and diabetes. Lab animals last longer on a very low-cal diet, and scientists are probing whether humans can benefit from this austerity. Or better yet, perhaps researchers can design molecules that deliver the gain of calorie reduction without the pain. Scientists are also focusing on which parts of the cell incur damage as we age and how growth and reproduction tie in to longevity. The speed of the next round of advances will depend on whether movers and shakers in funding organizations recognize the importance of the research and are willing to pay for it.     

Oxygen? No thanks, I'm on a diet

In yeast and worms, mutations that extend longevity appear to simulate starvation conditions. The daf-2 pathway in worms plays a major role in life-span extension and in entry into the starvation-resistant and low-metabolism dauer phase. In a recent study published in Science Express on 13 June 2002, researchers screened for Caenorhabditis elegans mutants that survive in a low-oxygen environment and identified a number of daf-2 mutants that are resistant to hypoxia. The implications of these results are discussed in this Perspective.     

The Built Environment,Health, and Longevity

Abstract

This paper reviews and integrates interdisciplinary literature that investigates the influence of the built environment on the subjective and objective health status of older persons that may improve their quality and quantity of remaining years of life. The development, expansion and synthesis of person-environment and ecological models provides the theoretical foundation. Central to this discussion is the identification and elaboration of salutogenic and pathogenic pathways (Antonovsky, 1979) through which the built environment may influence health, functioning and longevity. Research and knowledge drawn from literature on relocation, housing characteristics and well-being, the meaning of home, delay of institutionalization, technological devices, falls and other injuries, and healthy communities is used to demonstrate environmental pathways to health and longevity.     

Subfield history: use of model organisms in the search for human aging genes

The National Institute on Aging (NIA) started a program in 1993 to identify genes involved in the regulation of longevity in a variety of species, including yeast, nematodes, fruit flies, and mice. The initial success of this program has attracted the interest of many investigators working with these organisms. Of primary interest are single-gene mutants that have identified genes and processes involved in longevity regulation across species. These processes include the insulin-like signaling pathway, stress resistance, and most recently, chromosome and nuclear architecture. Mutations in genes that regulate these processes indirectly are also being identified in this program. The ultimate goal of this program is to extend these results to humans to identify the major biological risk factors for age-related decline of function in human physiological systems.     

Change resistance moderates existence and longevity biases

Evidence has been found for existence and longevity biases—inferences of goodness from prevalence or longevity. We argue these biases actually emerge among change-resisting individuals. Our evidence suggests change-accepting individuals can even demonstrate a reversal of these biases. In two studies, change-resisting individuals’ attitudes were suggestive of existence and longevity biases while change-accepting individuals significantly reversed this pattern by evaluating long-standing or prevalent objects less favorably. Finally, we reanalyzed data from the existence and longevity biases literature previously reported in Social Influence. We found Americans identifying as more Republican—thus theorized as more change-resisting—were those who favored a long-standing practice. Altogether, we argue that existence and longevity biases emerge depending on individuals’ change resistance, indicating an important theoretical expansion.     

Does anti-aging equal anti-microbial?

Aging is the dominant risk factor for human disease in developed countries. Could it be that a wide variety of disease states all have their origins in a common mechanism? Major signaling pathways that determine the rate of aging, such as the insulin/insulin-like growth factor 1 (IGF-1) pathway, might give clues to the nature of this major disease risk factor. It has now been shown that insulin/IGF-1 signaling influences Caenorhabditis elegans resistance to bacteria in such a way that long-lived worms are stress-resistant and slow to succumb to infection. Perhaps enhanced innate immunity is a feature of genetically determined longevity.     

Time matters: the potential and pitfalls of using mixed methods approaches in longitudinal program evaluation

While social programs are often assessed using short-term impact studies, longitudinal designs allow evaluators to capture change over time, identify longer-term outcomes, adapt instruments, and better understand participants in transition. A mixed methods design can be critical in understanding these dynamics; yet there is a lack of literature exploring the practical considerations of planning and conducting qualitative and quantitative data collection and analysis within longitudinal studies. This paper examines two different mixed methods frameworks used in a 5-year evaluation of three youth entrepreneurship programs in East Africa. We show how the evaluation team dealt with unique challenges across methods and over time, and how the design ultimately facilitated a richer understanding of program impacts and processes. Considerations for conducting this type of study are explored, related to the impact of longevity on analysis and research staff. Successfully using a longitudinal mixed methods approach requires researchers to be strategic and reflexive, and work in close collaboration.     

On trial

As researchers uncover basic mechanisms that underlie aging, they hope that lessons learned from mice, worms, flies, and other lab denizens will apply to people. Making that leap requires a new set of scientific approaches, from observational studies to the most rigorous of tests, the double-blind, randomized, placebo-controlled clinical trial. Navigating this unique scientific terrain presents new obstacles for basic-science researchers but can provide the ultimate payoff.     

Murine models of life span extension

Mice are excellent experimental models for genetic research and are being used to investigate the genetic component of organismal aging. Several mutant mice are known to possess defects in the growth hormone/insulin-like growth factor 1 (GH/IGF-1) neurohormonal pathway and exhibit dwarfism together with extended life span. Their phenotypes resemble those of mice subjected to caloric restriction. Targeted mutations that affect components of this pathway, including the GH receptor, p66Shc, and the IGF-1 receptor (IGF-1R), also extend life span; mutations that affect IGF-1R or downstream components of the pathway decouple longevity effects from dwarfism. These effects on life span may result from an increased capacity to resist oxidative damage.     

PASSAGE THROUGH MIDLIFE:

Life course researchers have recently examined the effects of normative and non-normative pathways into adulthood but little theoretical or empirical attention has been directed at the manner and type of transitions through the middle years of the life span for women. Women in midlife typically watch their last child leave the home and significant numbers also experience the dissolution of their marriages, either by divorce or widowhood. Using data from thirteen waves of the University of Michigan Panel Study of Income Dynamics, we find that the occurrence, sequencing, and timing of these two events greatly affect both women's labor force attachment and their economic well-being. These findings suggest new directions for conceptualizing midlife transitions for women.     

Caloric restriction in trans

Caloric (or dietary) restriction (CR) is the most potent, robust, and reproducible known means of extending longevity and decreasing morbidity in laboratory mammals. Two of the major questions faced by researchers in this field are the applicability to humans and the biochemical mechanism(s) involved in the actions of CR. Studies in nonhuman primates are beginning to address the former; studies in phylogenetically lower organisms such as yeast and Drosophila are beginning to address the latter. de Cabo and colleagues now provide evidence that some aspects of CR can be reproduced in mammalian tissue culture cells exposed to sera from rats and monkeys subjected to CR. This work presents the initial development of a new model with which to approach mechanistic studies of CR and provides a new form of direct evidence that CR exerts at least some of its effects in trans.     

LONGEVITY AND PUBLIC OLD-AGE PENSIONS

Using an overlapping generations model with endogenous but uncertain longevity, this article analyzes the effects of public old-age pensions on longevity choice and capital accumulation. When agents are not altruistic, increases in old-age pensions are longevity-neutral for golden rule economies and longevity-decreasing if interest rates exceed population growth, and saving effects are strictly negative. When agents are altruistic, longevity is independent of old-age pensions regardless of the interest rate–population growth relation. On the other hand, the longevity effect of a price subsidy on longevity extending expenditures or an advance in longevity extending technology is positive.(JEL H5 , J1 )     

Ticking fast or ticking slow, through Shc must you go?

Circumstantial evidence places the p66 isoform of the adapter protein Shc in a position to mediate the accelerated aging phenotype displayed by mice expressing shortened forms of the tumor suppressor protein p53. We present a model in which p66(shc) may be responsible for integrating signals from the p53 pathway with signals from the insulin-like growth factor-1/Daf pathway in mammals. A full understanding of how interactions between p53 and p66(shc) affect longevity will require the production of animals with mutations in the genes encoding both proteins.     

The longevity gender gap: are telomeres the explanation?

In this Perspective, we focus on the greater longevity of women as compared with men. We propose that, like aging itself, the longevity gender gap is exceedingly complex and argue that it may arise from sex-related hormonal differences and from somatic cell selection that favors cells more resistant to the ravages of time. We discuss the interplay of these factors with telomere biology and oxidative stress and suggest that an explanation for the longevity gender gap may arise from a better understanding of the differences in telomere dynamics between men and women.     

Allelic variation and human longevity

Human longevity is a complex phenotype with a strong genetic contribution. The search for allelic variation that impacts on longevity often involves population-based association studies of long-lived individuals (centenarians and nonagenarians) and younger controls. A major methodological problem with this approach is that the cases and controls in these experiments are often born several generations apart. The inherent absence of "age matching" can lead to serious misinterpretations. For example, allele frequency differences between long-lived individuals and younger controls may not reflect an effect on longevity but rather a change in population structure over time or different gene-environment interactions across generations.     

The unusual genetics of human longevity

In no species other than humans do cultural, social, and biological factors interact with each other in modulating complex phenotypes. Thus, the identification of genetic factors that affect human longevity is a true challenge. The model of centenarians provides us a unique opportunity to tackle this challenge. In this Perspective, we discuss some recent findings (the impact of geography and demography on the longevity phenotype, the relationship between longevity and homozygosity, the role of the nuclear-mitochondrial genome cross-talk) by which new ideas are suggested, such as the concept of a complex allele timing as a pivotal process in modulating the probability of achieving longevity.     

Complex Families and Late‐Life Outcomes Among Elderly Persons: Disability,Institutionalization, and Longevity

The authors examined the effects of marital status and family structure on disability, institutionalization, and longevity for a nationally representative sample of elderly persons using Gompertz duration models applied to longitudinal data from 3 cohorts of the Health and Retirement Study (N = 11,481). They found that parents with only stepchildren have worse outcomes than parents with only biological children. Elderly mothers with only stepchildren become disabled and institutionalized sooner, and elderly men with only stepchildren have shorter longevity relative to their counterparts with only biological children. The effect of membership in a blended family differs by gender. Relative to those with only biological children, women in blended families have greater longevity and become disabled later, whereas men in blended families have reduced longevity. The findings indicate that changing marital patterns and increased complexity in family life have adverse effects on late‐life health outcomes.     

Introduction: Human Longevity,Utopia, and Solidarity

Biomedical and geriatric technologies are having major impacts on the development and management of human longevity. Our contention in this special issue is that longevity should be considered as a point of departure for new forms of politics in which social sciences, in particular sociology and politics, can play an important role. In this introduction, we argue that emerging consumer markets in biomedicine are incrementally redefining the relationship between old age and society. Techno‐economic transformations are creating new sites of vulnerability that are masked by medical utopias of good health and “living forever.” In this context, it is unlikely that such technologies will be able to overcome inequalities in distribution and may well exacerbate various forms of injustice. By drawing on notions of institutional precariousness and scarcity, we conclude that to maintain any degree of social solidarity, increasing longevity will force the emergence of a “sociology of limits.”